This proposal will provide the candidate with the means of achieving the long-term goal of gaining independence as a clinical researcher in hepatology through a research proposal, structured mentoring, and methodological training. The candidate, Dr. Steven Zacks, is an Assistant Professor in the Division of Digestive Diseases. He and his mentors, Drs. Robert Sandler and Michael Fried, propose a combined didactic and clinical research experience, to foster Dr. Zacks' demonstrated interest in clinical research. As part of the training the candidate proposes to study the significance of hepatic steatosis on the highly variable natural history of hepatitis C (HCV). Because HCV can progress to cirrhosis with liver failure and death, it is important to target therapy to patients who are most likely to progress to cirrhosis. The candidate hypothesizes that HCV patients with steatosis on biopsy have nonalcoholic fatty liver disease in addition to HCV, leading to increased fibrogenesis. The specific aims of this study are to develop a well-characterized cohort of chronic HCV patients with and without steatosis on biopsy and to compare the prevalence of insulin resistance, markers of oxidant stress and fibrogenesis in chronic HCV patients with and without steatosis on biopsy. The proposed study will give the candidate valuable experience in the design of clinical studies, study management, data analysis, and manuscript preparation. The study will complement the didactic training at the UNC School of Public Health he has planned during the term of the award. The School of Public Health is a nationally recognized institution with an excellent graduate program in epidemiology. His sponsors have outstanding track records in mentoring and clinical research. Dr. Robert Sandler has a longstanding interest in training gastroenterologists to be outcomes researchers and will serve as the candidate's methodologic mentor. Dr. Michael Fried, an experienced clinical investigator in viral hepatitis, will be the candidate's clinical mentor. The candidate will have the wealth of clinical research resources at UNC available to him, including the NIH funded Center for Gastrointestinal Biology and Disease and the GI Epidemiology Group. The candidate has received formal training in the responsible conduct of research through the General Clinical Research Center. The UNC Department of Medicine is committed to providing the candidate with the protected time and resources to foster his career development.